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Metallo-β-Lactamases: Structural Features, Antibiotic Recognition, Inhibition, and Inhibitor Design

Journal

CURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume 13, Issue 10, Pages 1242-1253

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/15680266113139990011

Keywords

beta-Lactamase; antibiotics; resistance; new Delhi metallo-beta-lactamase

Funding

  1. National Natural Science Foundation of China [31200547]
  2. Doctoral Program Foundation of Institutions of Higher Education of China [20090073120079, 20110073120078]
  3. China Postdoctoral Science Foundation [20110490068]
  4. Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry

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Owing to their ability in destroying or slowing down the growth of bacteria, antibiotics have been widely used to treat the bacterial infections. However, because of the long-term and irresponsible use of antibiotics, resistance to antibiotics has become a serious problem directly threatening the public health worldwide. To fight against and resist lactam antibiotics, bacteria usually employed beta-lactamases, especially the metallo-beta-lactamases, to hydrolyze the C-N bond of the beta-lactam ring so as to inactivate the antibiotics. In this minireview, we are to summarize the structural features of the metallo-beta-lactamases, as well as their antibiotic binding modes and resistance mechanisms, in hopes that the discussion and analysis presented in this paper can stimulate new strategies to overcome the resistance problem and find novel inhibitors against the metallo-beta-lactamases.

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